New Tools and Targets: Optimizing Emergency Care for Neurotrauma Patients

Traumatic brain injury (TBI) results in approximately 4.8 million emergency department (ED) visits in the United States annually.1 Neurotrauma patients are highly heterogeneous, ranging from asymptomatic individuals who request an evaluation after an accident or impact to those with severe, non-survivable injuries. Many of the basics for initial management and evaluation of TBI remain consistent, including obtaining an accurate Glasgow Coma Scale (GCS) score and avoiding low oxygen levels and low blood pressure, said Halinder Mangat, MD, associate professor in the department of neurology and a neurocritical care specialist with The University of Kansas Health System and director of research at the Brain Trauma Foundation (BTF), which publishes influential clinical guidelines for TBI.2 Yet several evolving and emerging areas are relevant to emergency physicians (EPs), several of which are outlined in updated best practice guidelines from the American College of Surgeons (ACS) released in October 2024.3 These include the use of blood biomarker tests, quantitative pupillometry, and updates to monitoring targets. Biomarkers May Reduce the Need for Neuroimaging in Mild TBI One of the most significant updates in recent years is the availability of blood biomarker tests for mild TBI, said Natalie Kreitzer, MD, associate professor of emergency medicine and neurocritical care at the University of Cincinnati College of Medicine. In April 2024, the US Food and Drug Administration approved Abbott's i-STAT TBI cartridge to help evaluate patients up to 24 hours after an injury.4 The test measures levels of two proteins released when neurons are injured, serum glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and can deliver results at the bedside within 15 minutes. The ALERT-TBI study found that a cutoff of 30 pg/mL for GFAP and 360 pg/mL for UCH-L1 had a sensitivity of 95.8% and a specificity of 40.4% for the prediction of acute traumatic intracranial injury.5 Given that approximately 91% of head CT scans used to evaluate TBI in the ED each year are negative, these tests hold significant promise for screening out low-risk patients, said Frederick Korley, MD, PhD, professor of emergency medicine and associate chair of research at the University of Michigan, where the tests are being used for that purpose.6 More widespread implementation will likely depend on additional research in the field, including cost-effectiveness studies. In the meantime, decision rules, such as the Canadian CT Head Rule, along with steps such as institution- or department-specific targets may help reduce unnecessary neuroimaging, Dr Kreitzer said. Shifting Targets for Clinical Parameters in Moderate to Severe TBI In moderate to severe TBI, maintaining overall homeostasis is critical to optimizing oxygen delivery and avoiding secondary brain injury, said Tanya Egodage, MD, trauma surgeon at Cooper University Health Care and assistant professor of surgery at Cooper Medical School of Rowan University. Recent research has prompted updates in several clinical parameters applicable to patients in the ED. Take systolic blood pressure (SBP): A large prehospital study published in JAMA Surgery showed a linear decrease in mortality risk for every 10-point increase in SBP. As a result, prehospital guidelines issued by the BTF in 2023 and the ACS guidelines now both recommend targeting an SBP of 110 mmHg and above, an increase from 90 mmHg.7,8 There's also a potential shift on the horizon for hematology monitoring and transfusion strategy. While ACS and other existing guidelines currently recommend a hemoglobin target of ≥7 g/dL, results from the HEMOTION and TRAIN trials, both published last year, suggest that TBI patients may do better with liberal transfusion strategies, initiated at a hemoglobin level of ≤9 or ≤10 g/dL.9,10 Improving Precision with Quantitative Pupillometry Assessing pupillary light response is a longstanding component of neurological examination. Quantitative pupillometers, small, inexpensive handheld devices, have emerged as an option to obtain more precise readings and reduce inter-observer variability.11 Often, the output, which includes variables such as amplitude, latency, constriction, and dilation velocity, is calculated into an index, such as the Neurological Pupil Index (NPi). The multicenter ORANGE study found that an NPi score of less than 3 was strongly associated with increased mortality and poor neurological outcomes six months after a TBI.12 “It's something I would encourage emergency departments to use, particularly because some of those decisions will guide whether the patient is a candidate for surgery or ICP [intracranial pressure] monitoring and other things further down the road, particularly if you're working in an emergency department where you have to transfer those patients out,” Dr Kreitzer said. Recent Updates in Pharmacotherapy Posttraumatic Seizure Prophylaxis Early post-traumatic seizures (PTS) occur in as many as 10% of patients and are associated with longer hospital and intensive care unit (ICU) admissions, ventilation, and worse outcomes at 24 months.13 While the default has been to start antiseizure medication prophylaxis with all patients who have a positive brain CT, the new ACS guidelines recommend considering phenytoin or levetiracetam for 7 days in the presence of these risk factors: penetrating injury, depressed skull fracture, subdural hematoma, intracranial hemorrhage, cortical contusions, a GCS score of less than 10, and immediate seizure. Anticoagulation Reversal TBI patients on anticoagulants should be carefully assessed, and reversal therapy should be initiated to minimize the expansion of the injury in those who may need emergent surgery. In addition to drug-specific reversal agents, consider activated charcoal for patients whose previous dose was administered two hours earlier or less. Antibiotic Prophylaxis In moderate to severe TBI, symptoms of inflammation and infection may overlap, including fever, elevated white blood cell count, coughing, and shortness of breath. “It can be challenging to tease out what is infection and what is the brain injury itself,” Dr Kreitzer said. If EPs suspect that pneumonia or another infection contributed to a fall, treating empirically with a broad-spectrum antibiotic may be warranted. Tissue testing is typically more appropriate in the ICU; even in cases of penetrating brain injury, evidence doesn't support taking wound cultures before admitting patients. “What grows out is never represented by the samples you got in the emergency department,” Dr Mangat said. Counseling Patients with Mild TBI Data from the Track TBI networks show many patients who have mild TBI, and often a negative CT, go on to have persistent symptoms. “What patients hear is, ‘You're fine,’” Dr Korley said. “They go home and they're having difficulty concentrating, they're having difficulty sleeping, they can't focus, and they just find themselves super irritable. Then there's a disconnect.” To bridge this gap, EPs can advocate for systems of follow-up care by neurologists or other specialists, Dr Kreitzer said. They can also ensure that, even in patients with multi-system injury, TBI is diagnosed and patients are provided with detailed discharge instructions, such as those available from the Centers for Disease Control and Prevention (CDC).14 That way, patients leave the ED empowered: “You're not making it up. You did have a brain injury, and some of these symptoms you're having can be a result of the brain injury,” Dr Korley said. “That acknowledgment can be powerful, and that's a role that we in emergency medicine need to do a good job of playing.”

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